出版社：American Society for Biochemistry and Molecular Biology
摘要：The mitochondrial phospholipid cardiolipin is required for optimalmitochondrial respiration. In this study, cardiolipin molecularspecies and cytochrome oxidase (COx) activity were studied ininterfibrillar (IF) and subsarcolemmal (SSL) cardiac mitochondriafrom Spontaneously Hypertensive Heart Failure (SHHF) and Sprague-Dawley(SD) rats throughout their natural life span. Fisher Brown Norway(FBN) and young aortic-constricted SHHF rats were also studiedto investigate cardiolipin alterations in aging versus pathology.Additionally, cardiolipin was analyzed in human hearts explantedfrom patients with dilated cardiomyopathy. A loss of tetralinoleoylcardiolipin (L4CL), the predominant species in the healthy mammalianheart, occurred during the natural or accelerated developmentof heart failure in SHHF rats and humans. L4CL decreases correlatedwith reduced COx activity (no decrease in protein levels) inSHHF cardiac mitochondria, but with no change in citrate synthase(a matrix enzyme) activity. The fraction of cardiac cardiolipincontaining L4CL became much lower with age in SHHF than in SDor FBN mitochondria. In summary, a progressive loss of cardiacL4CL, possibly attributable to decreased remodeling, occursin response to chronic cardiac overload, but not aging alone,in both IF and SSL mitochondria. This may contribute to mitochondrialrespiratory dysfunction during the pathogenesis of heart failure.Supplementary key words phospholipids • mitochondria • linoleic acid • cytochrome oxidase • congestive heart failure • cardiomyopathy • aging
